What is the pathophysiology of glomerulonephritis following a streptococcal (strep) infection?

Pathophysiology of Post-Streptococcal Glomerulonephritis

The primary pathophysiology of post-streptococcal glomerulonephritis involves immune complex formation and deposition in the glomeruli, causing inflammation in the glomerulus and subsequent kidney damage. 1, 2

Immune-Mediated Mechanism

• Post-streptococcal glomerulonephritis (PSGN) is an immune complex-mediated disease that occurs 1-3 weeks after streptococcal pharyngitis or 4-6 weeks after impetigo 1
• Streptococcal antigens trigger the formation of immune complexes (antigen-antibody complexes) that deposit in the glomerular tissue 1, 3
• These immune complexes activate the alternative complement pathway, leading to inflammation and kidney injury 4, 5
• The disease is characterized by low C3 complement levels (typically returns to normal within 8-12 weeks) with normal C4 levels 1

Specific Streptococcal Antigens Involved

• Nephritogenic strains of group A beta-hemolytic streptococci produce specific antigens that are implicated in PSGN 3
• Two leading streptococcal antigens involved in pathogenesis:
  • Nephritis-associated plasmin receptor (identified as glyceraldehyde-3-phosphate dehydrogenase) 5
  • Cationic cysteine proteinase streptococcal pyrogenic exotoxin B 5

Histopathological Changes

• Diffuse proliferative glomerulonephritis with enlarged glomerular tufts due to hypercellularity 5
• Proliferation of endothelial and mesangial cells 5
• Immune complex deposition in the glomeruli visible on immunofluorescence 1
• In severe cases, crescentic formation may occur 6

Clinical Manifestations

• The immune complex-mediated inflammation leads to the classic nephritic syndrome presentation:
  • Hematuria (microscopic or macroscopic) with red blood cell casts 1, 7
  • Proteinuria (sometimes reaching nephrotic range) 1, 7
  • Hypertension due to fluid retention 1, 7
  • Edema, particularly facial edema 7
  • Impaired kidney function 7

Management Implications

• Treatment focuses on eliminating streptococcal infection with penicillin or erythromycin (if penicillin-allergic) to decrease antigenic load 6, 1
• Supportive care for nephritic syndrome includes diuretics, antihypertensives, and sodium restriction 6, 1
• Corticosteroids are only considered for severe crescentic disease based on anecdotal evidence 6, 1
• Most cases resolve spontaneously with supportive care 5

Diagnostic Considerations

• Persistently low C3 beyond 12 weeks may indicate an alternative diagnosis such as C3 glomerulonephritis 1
• Kidney biopsy is rarely needed unless there is diagnostic uncertainty, atypical presentation, or rapidly progressive disease 1, 4

Understanding this immune complex-mediated pathophysiology helps guide appropriate management, which primarily involves treating the underlying streptococcal infection and providing supportive care for the nephritic syndrome manifestations.